Lack of effect of a pneumonia clinical pathway on hospital-based pneumococcal vaccination rates.
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5-Lipoxygenase and leukotriene B(4) receptor are expressed in human pancreatic cancers but not in pancreatic ducts in normal tissue.
The 5-lipoxygenase (5-LOX) pathway is critical for pancreatic cancer cell growth and escape from apoptosis. Inhibition of 5-LOX blocks proliferation and induces apoptosis in human pancreatic cancer cells. However, the expression of 5-LOX and its downstream signaling pathway have not been investigated in human pancreatic adenocarcinoma. Reverse transcriptase-polymerase chain reaction revealed expression of 5-LOX mRNA in all pancreatic cancer cell lines tested including, PANC-1, AsPC-1, and MiaPaCa2 cells, but not in normal pancreatic ductal cells. The expression of 5-LOX protein in pancreatic cancer cell lines was demonstrated by Western blotting. Finally, 5-LOX up-regulation in human pancreatic cancer tissues was verified by intense positive staining in cancer cells by immunohistochemistry. Staining for the 5-LOX protein was particularly evident in the ductal components of the more differentiated tumors but not in ductal cells in normal pancreatic tissues from cadaver donors. Immunohistochemistry also revealed strong staining of cancer tissues with an antibody to the receptor of the downstream 5-LOX metabolite, leukotriene B(4). The current study demonstrated marked expression of 5-LOX and the leukotriene B(4) receptor in human pancreatic cancer tissues. These findings provide further evidence of up-regulation of this pathway in pancreatic cancer and that LOX inhibitors are likely to be valuable in the treatment of this dreadful disease.
Arachidonate 5-Lipoxygenase↗
Wnt signaling during development of the gastrointestinal tract.
Wnt signaling pathways have been demonstrated to play important roles in controlling tissue patterning and cell proliferation. In the gastrointestinal tract, mutations that lead to activation of the canonical Wnt pathway through beta-catenin result in familial and sporadic colon cancers. The downstream transcription factor Tcf4 is required to maintain the proliferative stem cell compartment in the crypts of the small intestine. Activation of TCF-dependent transcription is a good correlate to neoplastic transformation. Despite its association with cancer in the colon, little is known of the role for Wnt signaling during development and patterning of the gut tube. We conducted a comprehensive expression screen for Wnt signaling components during different stages of gut development in the chick. Conserved expression patterns of these genes indicate that they likely play essential roles in gut morphogenesis. Based on the expression profiles of putative components of each pathway, we are able to postulate specific roles for the various pathways during gut development. Predictions of roles for canonical signaling in the developing gizzard, duodenum, and large intestine in chick were tested by viral misexpression of dominant-negative (DN) forms of the downstream cofactors Tcf4 and Lef1. In the chick, Tcf4 is expressed in the posterior gizzard mesoderm. Misexpression of DN-Tcf4 in the splanchnic mesoderm resulted in the failure of the gizzard epithelium to form microvilli. Lef1 is expressed in the chick duodenum and large intestine mesoderm. Viral misexpression of DN-Lef1 resulted in diminished mesoderm and overproliferation of the large intestine endoderm, leading to stenosis of the lumen. The results from these misexpression studies in the chick, together with evidence from colorectal lesions, indicate that the canonical Wnt pathway plays critical roles in balancing cell proliferation versus cell differentiation during gut development. The expression profiles of the Wnt signaling components presented in this paper should prove valuable in deciphering additional roles of the Wnt pathways during patterning of the vertebrate gut tube.
Animals↗
The role of the p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and phosphoinositide-3-OH kinase signal transduction pathways in CD40 ligand-induced dendritic cell activation and expansion of virus-specific CD8+ T cell memory responses.
Mature dendritic cells (DCs) are central to the development of optimal T cell immune responses. CD40 ligand (CD40L, CD154) is one of the most potent maturation stimuli for immature DCs. We studied the role of three signaling pathways, p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and phosphoinositide-3-OH kinase (PI3K), in CD40L-induced monocyte-derived DC activation, survival, and expansion of virus-specific CD8(+) T cell responses. p38 MAPK pathway was critical for CD40L-mediated up-regulation of CD83, a marker of DC maturation. CD40L-induced monocyte-derived DC IL-12 production was mediated by both the p38 MAPK and PI3K pathways. CD40L-mediated DC survival was mostly mediated by the PI3K pathway, with smaller contributions by p38 MAPK and ERK pathways. Finally, the p38 MAPK pathway was most important in mediating CD40L-stimulated DCs to induce strong allogeneic responses as well as expanding virus-specific memory CD8(+) T cell responses. Thus, although the p38 MAPK, PI3K, and ERK pathways independently affect various parameters of DC maturation induced by CD40L, the p38 MAPK pathway within CD40L-conditioned DCs is the most important pathway to maximally elicit T cell immune responses. This pathway should be exploited in vivo to either completely suppress or enhance CD8(+) T cell immune responses.
CD40 Ligand↗
Outcome of a clinical pathway for discharge within 48 hours after laparoscopic gastric bypass.
BACKGROUND: The benefits of laparoscopic gastric bypass (LGB) include decreased pain, quicker recovery, and shorter hospital stay. Our hypothesis was that a clinical pathway for 48-hour discharge after LGB can be implemented safely. METHODS: Charts of patients undergoing LGB were retrospectively reviewed to assess our prospectively placed clinical pathway. Patients were discharged within 48 hours if they met the criteria of the pathway. RESULTS: There were 104 patients who underwent LGB with no intraoperative conversions. Complications included 5 leaks, 5 reoperations, and no mortality. In our series, 76% (n=79) of patients were discharged within 48 hours. Gender and body mass index (BMI) did not differ between those who were discharged in 48 hours and those who were not (P=not significant). No patient who was discharged in 48 hours required return before their scheduled appointment. CONCLUSIONS: A majority of patients after LGB can be discharged safely in 48 hours. A formal clinical pathway helps decrease hospital stay without adverse patient outcome.
Adolescent↗
Long-term outcomes of clinically significant vascular rings associated with congenital tracheal stenosis.
AIM: Congenital tracheal stenosis (CTS) associated with vascular rings (VRs) is considered a secondary condition, but relative indications for selective VRs or combined VR and CTS repairs are unclear. Here, we report long-term outcomes after VR repair associated with tracheal narrowing (TN). METHOD: Retrospective analysis of patients admitted to a single institution with VR from 1982 to 2004. Of 131 patients with VR (Cardiac Registry Database), 29 (19 males, 10 females; age range, 0 days-4 years) associated with symptomatic TN. Patients were followed until age 18 years. RESULTS: One hundred thirty-one patients with VR were categorized into 3 treatment groups. There were 102 patients with VR with no symptomatic TN treated by VR repair (4 deaths, 4% mortality). Of the 29 patients with VR + TN symptoms, 16 were treated by selective VR repair (mean age, 5.3 months; range, 17-288 days) with 3 deaths (19% mortality) and 13 underwent combined VR and CTS repairs (mean age, 11 months; range, 1 day-4 years) with 6 deaths (46% mortality), for an overall mortality of 31% (P < .01, chi2 test). Of the 102 patients with VR, 17 had intracardiac anomalies with 3 deaths (18% mortality). In contrast, 7 of 29 patients with VR with TN and intracardiac anomalies died (57% mortality); 3 patients in combined cardiac and CTS repairs (2 deaths, 67% mortality) and 4 in selective VR repairs (2 deaths, 50% mortality). CONCLUSIONS: Not all cases of TN associated with VR require combined repairs. The presence of TN and/or intracardiac anomalies in patients with VR, however, increases mortality risk to the repair of VR. Surgical decision requires individualized clinical pathway.
Abnormalities, Multiple↗
Perforated appendicitis in children: is there a best treatment?
PURPOSE: This study was performed to provide outcome data for the development of evidenced-based management techniques for children with appendicitis in the authors' hospital. METHODS: This is a retrospective analysis of 1,196 consecutive children with appendicitis over a 5-year period (1996 to 2001) at a metropolitan hospital. RESULTS: The median age was 9 years (7 months to 18 years). The perforation rate was 38.9%, and the nonappendicitis rate was 5.6%. Predictors of perforation included age less than 8 years, Hispanic ethnicity, generalized abdominal tenderness, rebound tenderness, and increased number of bands. In perforated cases, the median length of stay was 5 days, and the complication rate was 13.5%. There was no difference in complication rates related to type or timing of antibiotics or related to the individual surgeon. There was no difference in infection rates related to type of wound management. CONCLUSIONS: Children with perforated appendicitis are treated effectively by a less expensive broad-spectrum antibiotic regimen, expeditious operation by open or laparoscopic technique, primary wound closure, and postoperative intravenous antibiotics until they are afebrile for 24 hours and have a white blood cell count of less than 12,000/mm3. This approach is to be used in our prospective, randomized analysis of children treated on or off a clinical pathway.
Adolescent↗
Hospital care pathways for patients with schizophrenia.
Greater emphasis is being placed on reducing clinical variation in managing patient groups in the reformed National Health Service (NHS) in the United Kingdom (UK). The use of a care pathway to enable greater control over the process and quality of care will be explored for patients suffering from schizophrenia. The paper addresses three main factors for the development of care pathways for people suffering from schizophrenia: predictability of the illness; nature of standardized care; and role autonomy. It is argued that the diagnosis of schizophrenia does not lend itself easily to predicting care and treatment within a care pathway framework. However, a care pathway may bring other benefits, such as standardized care and a greater control over the delivery of care. Development and implementation of hospital care pathways require extensiv research. Qualitative research directions are advocated due to the possib difficulties of conducting an experimental study.
Case Management↗
Implementation of hospital care pathways for patients with schizophrenia.
AIM: This paper aims to discuss some of the issues for the implementation of care pathways for inpatients suffering from schizophrenia. This paper builds upon a previously published paper describing the development of the care pathway. BACKGROUND: The use of a care pathway may enable care to be delivered in a more efficient and effective way. Very little is known about the development or implementation of care pathways for mental health conditions. METHODS: Action research guided the process of implementation and led to 29 in-depth interviews. Participant observation and records of 15 working group meetings rounded the data analysis. FINDINGS: The nature of the study site changed dramatically over the course of the research programme with many staff leaving the ward. This led to many problems in implementing the care pathway including poor levels of morale and engagement; how the patients were admitted and managed on the care pathway; poor levels of documentation. CONCLUSIONS: The findings are particular to this research environment, although some wider issues could be applicable to other sites such as the nature of representing psychiatric work on the care pathway; the evidence-based practice movement and the role of the user and individualized care.
Adult↗
Do clinical pathways really improve clinical performance in mental health settings?
OBJECTIVE: Royal Brisbane and Women's Hospital (RBWH) Mental Health developed and trialled two clinical pathways on psychosis and depression between 2001 and 2003 with the aim of improving a range of clinical and financial parameters. There was a strong commitment from senior management, appropriate resources were allocated and there was adequate staff support. Following a 6-month trial, the pathways were reworked extensively and combined into an acute inpatient pathway. From October 2003 to 2004, we trialled the acute inpatient clinical pathway, and monitored clinical and financial parameters. CONCLUSION: Over this 12-month period, the acute inpatient clinical pathway failed to demonstrate improvement on a range of clinical and financial parameters and its use was ceased. This trial lends support to the view that the complexity, individuality and variability of mental disorders means that clinical pathways are not beneficial in mental health settings.
Acute Disease↗
National practice patterns for the care of the patient with total joint replacement.
PURPOSE: The purpose of this study was to determine national practice patterns for common nursing procedures related to the care of total hip and total knee patients. DESIGN: This was a comparative descriptive study utilizing a survey developed by the NAON Total Joint Special Interest Group. SAMPLE: Two hundred eight-seven valid surveys were completed by NAON members. FINDINGS: An average of 226 total knee replacements (TKR) and 183 total hip replacements (THR) were performed annually per facility. Data about perioperative practices, postoperative activity practices, use of equipment, anticoagulation practices, and discharge practices (including length of stay) were collected. IMPLICATIONS FOR NURSING PRACTICE: Knowledge of national practice patterns and incorporation of the information into clinical practice can reduce the patient's risk of unsafe or ineffective care while promoting positive patient outcomes. Nurses can use these data to adjust clinical pathways and practice standards to improve patient outcomes.
Arthroplasty, Replacement↗
Collaborative development of a clinical pathway for congestive heart failure.
Bon Secours Hospital, a 304-bed community hospital in Grosse Pointe, MI, decided to target high-volume and high-cost DRGs for clinical process improvement. Working collaboratively with members of the medical staff, the cardiac team set out to improve outcomes by reducing the non-value-added costs and the variations in the treatment of patients with congestive heart failure (CHF). A comprehensive program of care for these patients, that included the full continuum of care, from prevention to maintenance, is being developed, using a clinical pathway to manage the acute phase of treatment.
Cardiology Service, Hospital↗
Statistical and methodological issues in the evaluation of case management studies.
For the past 3 years, the nursing case management team at North Shore University Hospital in Manhasset, NY, has been involved in a project to implement more than 50 clinical pathways, which provide a written "time line" for clinical events that should occur during a patient's hospital stay. A major objective of this project was to evaluate the efficacy of these pathways with respect to a number of important outcomes, such as length of stay, hospital costs, quality of patient care, and nursing and patient satisfaction. This article discusses several statistics-related issues in the design and evaluation of such case management studies. In particular, the role of a research approach in implementing and evaluating hospital programs, the choice of a comparison (control) group, the exclusion of selected patients from analysis, and the problems of equating pathways with diagnosis-related groups are addressed.
Case Management↗
Continuous quality improvement for the clinical decision unit.
Clinical decision units (CDUs) are a relatively new and growing area of medicine in which patients undergo rapid evaluation and treatment. Continuous quality improvement (CQI) is important for the establishment and functioning of CDUs. CQI in CDUs has many advantages: better CDU functioning, fulfillment of Joint Commission on Accreditation of Healthcare Organizations mandates, greater efficiency/productivity, increased job satisfaction, better performance improvement, data availability, and benchmarking. Key elements include a database with volume indicators, operational policies, clinical practice protocols (diagnosis specific/condition specific), monitors, benchmarks, and clinical pathways. Examples of these important parameters are given. The CQI process should be individualized for each CDU and hospital.
Benchmarking↗
A nurse-led, patient-centred mitoxantrone service in neurology.
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system for which there is no known cure. There are licensed treatments available to influence the disease course, but for a small group of patients, progression of the disease may continue at an alarming rate. Mitoxantrone, a cytotoxic agent normally used in the treatment of cancer, has been shown to reduce disease activity in patients who have this more aggressive form of MS. However, the immunosuppressive action and side-effect profile of mitoxantrone mean that this drug should be used with caution. This article describes a MS nurse-led initiative where an evidence-based, integrated care pathway was designed to ensure a safe, high-quality service provision for this select patient group.
Antineoplastic Agents↗
Reflections on pain management: a case study.
This article discusses issues relating to pain management at the end of life. Through reflections on a case study of a single patient many aspects of pain management are highlighted. These include difficulties in assessing pain, the need to respect patient autonomy, out-of-hours concerns and the possible role of integrated care pathways. The need to be aware of the potential value of non-pharmaceutical approaches is also discussed.
Analgesia↗
Using care pathways in pressure area management: a pilot study.
Care pathways are a method of managing, delivering and documenting care. A pilot study of a care pathway system in pressure area management was conducted in two clinical areas. Results from this pilot study indicate that the pathway approach to pressure area management is both useful and valid as a means to enhance clinical decision-making and to facilitate comprehensive pressure area management and the completeness of care documentation. Implementation of the pathway requires a facilitator to provide support and education and to monitor and maintain the change process.
Critical Pathways↗
Laryngectomy clinical pathway: development and review.
OBJECTIVE: The goal of the study is to determine if the implementation of a protocol for the preoperative and postoperative care of patients receiving a laryngectomy for cancer of the larynx or hypopharynx (i.e., laryngectomy clinical pathway) reduced length and cost of hospital stay without increasing complication rates. DESIGN: This study is a comparison of the perioperative course of two groups of laryngectomy patients. Data were collected retrospectively from the records of patients operated on before the implementation of the clinical pathway as the institutional historical control. Comparison was made with data collected prospectively on patients operated on after the implementation of the clinical pathway. SETTING: The study was performed at a mid-sized teaching hospital associated with two regional cancer centres. All surgeries were performed by one of two otolaryngology-head and neck surgeons and residents under their supervision. METHODS: The demographic, patient, tumour, treatment, dietary, and complication data were analyzed. Fisher's exact (two-tailed) statistical test was used for parametric data and Wilcoxon scores for nonparametric data. MAIN OUTCOME MEASURE: The principal outcome measure was the length of postoperative inpatient stay. Secondary outcome measures were readmissions and postoperative complications. RESULTS: There was a statistically significant decrease of 6.7 days in the mean length of hospitalization in the clinical pathway group even when taking postoperative readmissions into account. There was no concomitant increase in surgical complications. The mean reduction in hospital cost per case was calculated to be $3,420 (Can). CONCLUSIONS: Application of a clinical pathway for patients receiving laryngectomy is both feasible and effective.
Case-Control Studies↗